RAPID 1,25(OH)(2)-VITAMIN-D-3 STIMULATION OF CALCIUM-UPTAKE BY RAT INTESTINAL-CELLS INVOLVES A DIHYDROPYRIDINE-SENSITIVE CAMP-DEPENDENT PATHWAY

The acute effects of 1,25-dihydroxy-vitamin D-3 (1,25(OH)(2)D-3) on Ca 2+ influx in isolated rat enterocytes were studied. The hormone signif icantly increased Ca-45(2+) uptake by the cells within 1-10 min in a s pecific dose-dependent manner (10(-11)-10(-9) M) since 25(OH)D-3 and 2 4,25(OH)(2)D-3 were devoid of activity. The effects of 1,25(OH)(2)D-3 were mimicked by the Ca2+ channel agonist BAY K8644 and completely abo lished by nifedipine (1 mu M) and verapamil (10 mu M). Incubation of d uodenal cells with 1,25(OH)(2)D-3 rapidly (1-5 min) increased cAMP lev els. Forskolin caused a rapid increase in Ca2+ uptake by enterocytes w hich was similar to the action of the hormone. Moreover, pretreatment of cells with the specific cAMP inhibitor Rp-cAMPS suppressed the chan ges in Ca-45 influx induced by 1,25(OH)(2)D-3. These results provide t he first evidence involving Ca2+ channel activation through the cAMP p athway by 1,25(OH)(2)D-3 in mammalian intestinal cells.